Global Effect of Sympathomimetic Drugs on the Vascular System

The sympathetic autonomous system works by the release of neurotransmitters that act on the adrenoreceptors, with their various types and subtypes. The effects produced can be mimicked by drugs that stimulate these receptors, known as sympathomimetics. Some sympathomimetics have a higher affinity for a certain receptor type or subtype while others are rather non-selective.

00:01
Now, when we take all of these together,
we have to look at multiple innervation systemsso that we can understand the overall effect.
00:09
So in the vascular system, it is acted upon by
alpha 1, alpha 2 and beta 2.
00:15
So, let's take a look at each of these
in this special circumstance.
00:22
The alpha 1 agonists. The prototypical alpha 1 agonist
is phenylephrine. It contracts smooth musclein the splanchnic blood vessels,
so that means the one that goes to the gut.
00:35
And it increases blood pressure by incresing
the total peripheral resistance.
00:41
Now, one of the side effects of phenylephrine
is reflex bradycardia.
00:47
Now, I'm going to spend a little bit of time to explain this.
00:52
We would think that an agonist of a sympathomimetic drug
or a sympathomimetic system would cause a fast heart rate.
00:59
But what we're talking about here is a very specific drug
that is only acting on blood vessels,it's not acting on the heart.
So the heart is free to respond however it wishes.
01:11
When the heart senses that the blood pressure is higher,
it will slow itself down,thinking that there's too much adrenaline around.
01:20
Right. So that's why you get reflex bradycardia
from phenylephrine.
01:26
The other issue too is that the baroreceptors also have
connections to the vagus nerve which innervates the heart,so the vagus nerve will actually slow down the heart as well.
That's why phenylephrine causes the reflex bradycardiaeventhough it's considered the sympathomimetic.
And the reason why is cause it's an alpha 1 agonist.
01:47
Okay. Does that sound like it make sense?
Alright, let's move on.
01:52
What about the alpha 2 agonist?
The classical alpha 2 agonist is clonidine.
02:01
Now, I just finished telling you that alpha 1 agonist
will increase the blood pressure,and now I'm going to tell you that alpha 2 agonist
are decreasing the blood pressure.
02:11
Why is that happening?
Well, let's take a look at the blood vessel itself.
02:16
Yes, alpha 2 agonist cause vasoconstriction.
And we sometimes use it topically in nasal sprays.
02:24
So, clonidine for example, or other alpha 2 agonist
can be sprayed up the nose when we're congestedand it causes some mild constriction of the blood vessels.
However, clonidine also crosses the blood brain barrier.
02:38
And it accumulates in the brain. And now what it's doing is
it's acting to reduce sympathetic outflow and blood pressure.
02:46
Why? Well, if you have an excessive amount of adrenaline
crossing through your system, and it's sensed by the brain,you know that the brain is saying "Uhh ohh, we're really in
trouble. We need to reduce our sympathetic outflow."So, it's taking advantage of a feedback loop.
That's why clonidine reduces blood pressure.
03:04
Now, I should mention very quickly that clonidine is not
our favourite form of blood pressure agent,I'm going to talk about it more in our hypertension lectures.
The problem with clonidine is because it acts centrally,you can also get orthostatic drops when you stand up.
03:22
Okay, let's go on to the beta 2 agonist. So, remember
that the beta 2 receptor is in the lungs, right?There's two lungs, one heart,
so beta 1 is heart, beta 2 is lungs.
03:33
Albuterol, salbutamol. Salbutamol is better known as ventalin.
There is going to be some vasodilation in the skeletal musclewith these drugs. But you have to usually take a very
high dose in order to achieve that.
03:47
There are maybe some reduction in blood pressure
with the usage of ventalin.
03:52
In general, I've never seen that in clinical practice.
03:55
There is some vasodilations in the lungs as well.
Cocaine is also an agonist.
04:03
And remember that cocaine, when taken in the nose
causes vasoconstriction.
04:09
Cocaine, as crack cocaine, causes vasodilation,
and that's why crack cocaine is absorbed so quickly,because where it's landing it's dilating the blood
vessels and getting into the blood much more quickly.
04:21
We are going to talk more about cocaine and crack
in our toxicology lectures.
04:27
So, let's talk about toxicity. With catecholamines,
they rarely cause clinical problems as medications.
04:36
It's quite rare because they're quite short lived. However,
I do want you to go back and read up on "pheochromocytoma".
04:42
It's a relatively rare kind of tumour of the adrenal gland.
And it's best done if you read it on your own in a textbook.
04:50
Dopamine. If you give excess amount of dopamine, you can
sometimes cause digital ischemia and mesenteric ischemia.
04:58
We kind of mentioned that in the case that I was talking
about earlier where you risk losing fingersand you risk causing infarcts of the bowel
with excess of levels of dopamine.
05:09
And finally, amphetamines and cocaine which I've very
briefly touched on and will cover later.

About the Lecture

The lecture Global Effect of Sympathomimetic Drugs on the Vascular System by Pravin Shukle, MD is from the course ANS - Pharmacology.

Included Quiz Questions

Which of the following sympathomimetic drugs will lead to an increase in total peripheral resistance?

Phenylephrine

Clonidine

Intermediate dose dopamine

Terbutaline

Albuterol

Clonidine typically is used for vasoconstriction of nasal blood vessels, but overall may lead to decreased blood pressure? What is the mechanism that allows this conflicting effect?

It acts centrally leading to a reduction in sympathetic outflow.

It vasodilates in smooth muscle but vasoconstricts in mucosal blood vessels via activation of different adrenergic receptors.

It only decreases blood pressure via orthostatic hypotension.

It works by diverting blood flow to the splanchnic vessels leading to overall decrease in blood volume.

It works via a reflex mechanism to decreased blood pressure.

Which of the following would you LEAST likely expect in a patient, on administration of phenylephrine?

All of the answers would be expected.

Increased blood pressure

Contraction of smooth muscle in splanchnic vessels

Reflex bradycardia

Increased total peripheral resistance

In the ICU, dopamine may be administered in high doses. What is the risk associated with dopamine administration in high doses?

Mesenteric and digital ischemia

Orthostatic hypotension

Inadequate diastolic filling time

Bronchoconstriction

Reflex bradycardia

Author of lecture Global Effect of Sympathomimetic Drugs on the Vascular System

Pravin Shukle, MD

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